Oxidative stress plays a pivotal role in the onset and progression of a wide range of human diseases, including neurodegenerative disorders, cancer, cardiovascular dysfunctions, metabolic diseases, and inflammatory conditions. The imbalance between reactive oxygen species and endogenous antioxidant defenses not only disrupts cellular homeostasis but also triggers molecular pathways that contribute to tissue damage and chronic pathology. In this context, medicinal chemistry offers unique opportunities to design, synthesize, and optimize molecular entities capable of modulating oxidative processes at different biological levels.

This Special Issue aims to gather cutting-edge contributions on the chemistry and pharmacology of compounds targeting oxidative stress, including direct radical scavengers, enzymatic modulators, redox-sensitive prodrugs, metal-based antioxidants, and molecules influencing redox signaling pathways. Emphasis will be placed on innovative chemical scaffolds, structure–activity relationships (SAR), mechanistic studies, computational approaches, and translational strategies that bridge molecular design with therapeutic potential. Nanotechnology-enabled delivery systems, which offer innovative strategies to enhance pharmacokinetics, will be also explored.

Original research articles, reviews, and perspective pieces are welcome, particularly those that explore novel antioxidative mechanisms, multi-target-directed ligands, biomarkers of oxidative damage, and drug discovery approaches integrating redox biology. By bringing together interdisciplinary expertise, this Special Issue seeks to advance the understanding of redox-driven diseases and stimulate the development of next-generation therapeutic agents that effectively modulate oxidative stress.

By integrating medicinal chemistry, redox biology, and nanotechnology, this Special Issue aims to stimulate interdisciplinary dialogue and foster the development of next-generation therapeutic strategies designed to effectively modulate oxidative stress in complex disease settings.